Cell-mediated immune responses, involved in delayed-type hypersensitivity, are responsible for the in vivo recognition and defense against infectious agents and play a major role in immune surveillance for homograft or tumor rejection. The aim of this study is to utilize established human lymphoid cell cultures (lymphoblasts), active in synthesizing differentiated cell products involved in the above responses, to investigate the factors affecting the frequency of spontaneous and induced mutations of leukocytes and the nature of the control mechanisms determining differentiated capability. The following specific problems will be examined: 1) Control mechanisms for synthesis of immunoglobulins, complement (C'3) and migration inhibitory factor(s) will be characterized in somatic cell hybrids between lymphoblast clones with alternate biosynthetic capabilities or ploidy levels and in lymphoblast/human fibroblast combinations, to study intraspecific cellular control of lymphoid functions; (2) The effect of chemical and physical mutagenic agents will be compared with various cell lines, clones and chromosomal (ploidy) variants, to determine the role of gene dosage and balance in modifying cellular mutability and survival frequencies; and (3) The involvement, activity and variability of DNA-repair will be studied in different euploid lymphoblast cell lines and in various clones with spontaneous or induced ploidy alterations, to assess the importance and variability of repair in modulating cellular aberrations and mutation frequencies following mutagenic damage. Electroimmunoassay ("rocket" electrophoresis) and immunofluorescence methods will be used to quantitate differentiated capabilities of various cell lines, mutants and hybrids. Alkaline sucrose gradients and autoradiography will be used to measure DNA-repairates and alterations in various cell lines and induced variants.